The present invention relates to a method for the treatment or prophylaxis of ocular inflammation by the administration of an anti-inflammatory agent and also provides compositions containing this agent and especially formulated for ophthalmic use.
The ophthalmic agent of the present invention is a member of the class of phenylacetic acid derivatives and the compounds employed as such agents have been disclosed in, for example, United Kingdom Pat. Specification No. 1,580,113 and the corresponding U.S. Pat. No. 4,161,538, United Kingdom Pat. Specification No. 2,002,762 and the corresponding U.S. Pat. No. 4,254,274, United Kingdom Pat. No. Specification No. 2,078,732 and the corresponding U.S. Pat. No. 4,400,534, European Pat. Publication No. 55,588, United Kingdom Pat. Specification No. 2,113,214 and the corresponding U.S. Pat. No. 4,461,912 and U.S. patent application Ser. No. 600,372, filed Apr. 16, 1984. Of these, United Kingdom Pat. Specification No. 2,078,732 describes the use of these phenylacetic acid derivatives for topical administration, whilst the remaining documents referred to disclose the use of the compounds for internal (i.e. oral or parenteral) use.
We have now discovered that these compounds can be used to prevent or inhibit inflammation of the eye. This is particularly surprising since anti-inflammatory compounds are not commonly capable of being used in such a variety of ways. For example, aspirin and many other analgesic anti-inflammatory agents may be administered systemically, usually by the oral route, but are not used for topical administration. On the other hand, methyl salicylate, which is used externally for rheumatic conditions, is considered too toxic for internal administration, and similarly compounds such as bendazac and bufexamac are normally only used externally. Moreover, phenylbutazone, ibuprofen and indomethacin, which are all well-known and commonly used anti-inflammatory agents, and which are cited in the above documents for comparative purposes, are all known to have adverse effects upon the eye. For example, phenylbutazone has been reported to cause conjunctivitis, toxic amblyopia, Stevens-Johnson syndrome, adhesion of lids to eyeballs, gross scarring of lids, corneal ulceration and scarring, vascularisation of the cornea, loss of vision and possible retinal haemorrhage [H. I. Silverman, Am. J. Optom., 49, 335 (1972)]. Indomethacin has been reported to cause mydriasis, diplopia and toxic amblyopia (H. I. Silveman, op. cit.), decreased retinal sensitivity and corneal deposits [C. A. Burns, Am. J. Ophthal., 66, 825 (1968)] and a variety of other corneal and retinal effects. Ibuprofen has been reported to cause a variety of visual defects, including toxic amblyopia [L. M. T. Collum and D. I. Bowen, Br. J. Ophthal., 55, 472 (1971)]. Accordingly, use of these compounds for treatment of eye disorders is hardly likely to be considered. There is, therefore, normally a clear distinction between anti-inflammatory agents employed for systemic, topical and ophthalmic use.
We have now surprisingly discovered that the aforementioned phenylacetic acid derivatives can be employed for the treatment of ocular disorders.